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Biomedical subjects

J L Sever

Publications and source records attributed to J L Sever.

At least 127 records · Page 7Linked to original sources

Infections in pregnancy: highlights from the collaborative perinatal project.

The longitudinal study of approximately 60,000 pregnant women was conducted at 14 major medical centers throughout the United States. Clinical data was obtained under prescribed protocols for each of the study women throughout their pregnancy, at delivery, and through the postpartum period. The children were followed with uniform examinations from birth through seven years of age. In addition blood samples were taken from the pregnant women at registration, every two months through pregnancy, at delivery, and six weeks postpartum. Cord blood samples were also taken from the children during the last half of the study. We have used this material from the Collaborative Perinatal Project for the investigation of the role of infections in the production of damage to the fetus and newborn. The frequency of clinically recognizing infection during pregnancy was determined and geographic variation was demonstrated. Serological tests were used to document certain diseases. The frequency of confirmed clinical cases per 10,000 were: rubella, 8; rubeola, 0.6; mumps, 10; varicella-zoster, 5. The epidemiology and clinical findings associated with infections were studied using serological methods. This has provided data on the frequencies of infections such as cytomegalovirus, herpes simplex, mumps, rubeola, respiratory syncytial virus, and others. The study of abnormal pregnancies and matched controls is in progress using serological techniques. A number of specific studies have been reported on infections including rubella, neonatal meningitis, cytomegalovirus, maternal urinary tract infections, and toxoplasmosis. Further testing is now in progress employing more sophisticated laboratory methods and more complete data analysis.

Child↗

Virus antibodies in the cerebrospinal fluid of multiple sclerosis patients detected with ELISA tests.

The enzyme-linked immunosorbent assay (ELISA) was used to determine levels of specific IgG antibodies against measles, rubella, vaccinia, corona (OC43) and mumps viruses in cerebrospinal fluid (CSF) and serum of 18 patients with clinically definite multiple sclerosis (MS), 8 patients with optic neuritis (ON), 27 patients with other neurological disease (OND), and 88 control subjects without central nervous system disease. Serum antibody levels were not significantly different between the four groups. Differences in the frequency and levels of CSF antibodies between the four groups were observed. Control patients had serum/CSF antibody ratios from 2.0 to 3.0 (log) with an average of 2.5 corresponding to a 320-fold difference between serum and CSF antibody levels. MS patients had ratios from 1.1 to 2.1 with an average of 1.6. The average was 2.0 for the ON patients. The average for the OND patients was similar to the controls. The altered serum/CSF ratios for several viruses within an individual patient was similar. These results suggest that nonspecific immunostimulation is responsible for the increased levels of CSF virus antibodies.

Antibodies, Viral↗

Persistent Varicella-Zoster virus infection in a human rhabdomyosarcoma cell line and recovery of a plaque variant.

Varicella-zoster virus (VZV) has been found to persistently infect the human rhabdomyosarcoma cell line A204. Infectious center assays and fluorescent antibody staining demonstrated continuous production of infectious VZV and viral antigen. The level of infection determined by fluorescent antibody staining was variable, and usually only a small percentage of the cells were capable of producing plaques in permissive fibroblasts. The extent of infection was similar in cell cultures passaged at split ratios of 1:2 or 1:10 and grown at 33 or 37 degrees C. VZV recovered from A204 cells several months after establishment of the persistent infection had markedly increased syncytia-forming activity as compared with the parental VZV grown in human diploid fibroblast cells and the three monkey kidney-derived cell lines Vero, CV-1, and MA104. The expression of this altered phenotype continued after serial passage of the cell-associated virus in human diploid fibroblast and Vero cells. Consequently, we designated the reisolated VZV as plaque variant A. The buoyant densities of VZV plaque variant A and VZV DNAs in CsCl gradients were indistinguishable.

Antigens, Viral↗

Microsticks as solid-phase carriers for enzyme-linked immunosorbent assays.

Microsticks are machine-tooled or molded pegs of plastic or stainless steel which were developed as solid-phase carriers for the enzyme-linked immunosorbent assay (ELISA). They consist of a stem, which can be coated with plastic to be used as the reactive surface, and a shaft designed for easy handling and labeling and for positioning the sticks in microtiter wells and transfer plates. Microsticks permit a wide selection of coating materials and afford the user greater control over quality and standardization of the solid-phase surface. Polycarbonate and nitrocellulose coatings were tested in ELISAs for antibodies to measles virus, toxoplasma, and human gamma globulin. The Microsticks were found to give reproducible, sensitive, and specific ELISA results and minimized problems due to lot-to-lot and batch-to-batch variations found with other plastic carriers.

Antibodies↗

Measles and canine distemper antibody. Presence in sera from patients with multiple sclerosis and matched control subjects.

Antibody to measles virus and canine distemper virus (CDV) was demonstrated in sera from patients with multiple sclerosis (MS) and from carefully matched control subjects. Elevated measles and CDV antibody titers were found in patients with MS when compared with the matched control subjects. The correlation between the measles and CDV antibody titers was quite high, suggesting that the antibody levels between the two viruses are very closely related. Based on the results of our study and a review of the literature, our conclusion is that the CDV antibody levels in patients with MS and matched control subjects are associated with occurrence of measles virus antibodies.

Antibodies, Viral↗

Herpesviruses and parkinsonism. Herpes simplex virus types 1 and 2, and cytomegalovirus antibodies in serum and CSF.

Antibodies against herpes simplex virus (HSV) types 1 and 2 and cytomegalovirus (CMV) were assayed with a microindirect hemagglutination (IHA) test in the serum of 67 pairs of patients with Parkinson's disease and controls. Cerebrospinal fluid from 30 pairs was assayed. All patient and control serum was tested with a radioimmunoassay (RIA) for antibodies against HSV type 1 subunit antigens. Serum IHA antibody level against HSV type 1 was increased in patients with Parkinson's disease and RIA antibody levels against the same viral antigen were significantly higher in the patients than controls. Herpes simplex virus type 2 and CMV serum antibodies were equal in the patient and control groups. Most of the CSF samples tested negatively for IHA; small and comparable numbers of the patients and controls had low antibody levels against HSV and CMV antigens.

Antibodies, Viral↗

Coronavirus antibodies in sera from patients with multiple sclerosis and matched controls.

Sera from patients with multiple sclerosis and carefully matched controls were tested for antibodies to three strains of coronavirus. There was no significant difference in the levels of antibody in the patients vs the controls. We conclude that unless the strains of coronaviruses recently reported to have been isolated from patients with multiple sclerosis express important serological differences from those used in these studies, coronaviruses are not associated with the cause of multiple sclerosis.

Animals↗

Micromethod for detection of oligoclonal IgG in unconcentrated CSF by polyacrylamide gel electrophoresis.

A micromethod to detect oligoclonal IgG from 50 microL of unconcentrated CSF was developed by using polyacrylamide gel electrophoresis in sodium dodecyl sulfate (SDS-PAGE). Of 17 patients with multiple sclerosis, oligoclonal bands were demonstrated in 16 instances (94%) by micro-SDS-PAGE and in 13 (76%) by agarose gel electrophoresis. The corresponding figures among 30 patients with optic neuritis were 16 (54%) and five (17%), respectively, and among ten patients with other neurological disease the figures were two (20%) and none, respectively. Thus, micro-SDS-PAGE is more sensitive than agarose gel electrophoresis for detection of oligoclonal IgG. The small volume of unconcentrated CSF that is required enhances the usefulness of this test.

Adolescent↗

Relationship between measles HI titers and an MS susceptibility gene.

Recently published studies of formal linkage analyses strongly suggest that a multiple sclerosis susceptibility (MSS) gene is linked to the HLA region of the sixth chromosome. The objective of this analysis was to investigate whether or not the gene has any demonstrable relationship to the immune status with regard to measles within members of multiple-case MS families. Family members were HLA-typed, and levels of antibodies to measles were determined using the hemagglutination inhibition assay. Since a specific, HLA-defined haplotype within each family is presumably a marker for the MSS gene, family members were characterized as either carrying [(+) controls] or not carrying [(-) controls] the MSS gene by the presence of this specific haplotype. Twenty families were entered into the analyses. Results revealed that the mean titer to measles was not different between (+) and (-) controls, and that MS cases had significantly higher titers than both control groups combined.

Age Factors↗

Evaluation of commercially available diagnostic test kits for rubella.

Three standard hemagglutination-inhibition (HAI) methods were compared with 11 commercially available diagnostic test kits for determination of immunity and serologic diagnosis of rubella using a panel of 100 sera. The three standard HAI methods involved removal of serum inhibitors with kaolin, heparin-MnCl2, or dextran sulfate-CaCl2. The HAI kaolin (Flow Laboratories, McLean, Virginia) and Rubelisa (Microbiological Associates Bioproducts, Walkersville, Maryland) kits gave the best specificity as judged by the absence of false-positive results. Rubacell (Abbott Laboratories, Chicago, Illinois), Rubindex (Ortho Diagnostics, Raritan, New Jersey), Fiax (International Diagnostic Technology, Santa Clara, California), and Rubesure (Calbiochem-Behring, La Jolla, California) gave the best sensitivity as judged by the absence of false-negative results. The kits with the highest degree of both specificity and sensitivity were HAI kaolin (Flow), HAI heparin-MnCl2 (Flow), Rubacell (Abbott), and Rubindex (Ortho). In paired sera from five patients with clinical rubella, seroconversions were shown by seven of the kits. One of the kits, Cordia R (Cordis Laboratories, Miami, Florida), showed no significant rise in antibody titer with one pair of sera. Antibody titers in the same serum varied widely between the different kits.

Animals↗

Comparison of hemagglutination inhibition test and enzyme-linked immunosorbent assay for determining antibody to rubella virus.

The hemagglutination inhibition test (HAI) and the enzyme-linked immunosorbent assay (ELISA) for detecting antibody to rubella virus were compared by testing 25 sets of paired sera taken before and after infection and 10 sets of sera taken during acute and convalescent stages of the disease and by screening 700 serum samples from the Collaborative Perinatal Project, NIH/NINCDS. The tests were found to be comparable in their ability to detect positive and negative sera, rises in titers, and seroconversions. When a purified antigen and carefully prepared reagents were used, ELISA was found to be as accurate and reliable as HAI. ELISA required no pretreatment of serum, could easily be automated, and was less time-consuming than HAI.

Antibodies, Viral↗

Changes in immune response during responses in MS patients.

Changes in clinical status and in two measures of immune function were followed for 21 months (median) in 106 multiple sclerosis (MS) patients and cohabitant controls. Antibody titers to measles, cytomegalovirus, and herpesvirus 1 and 2, and leukocyte migration inhibition indexes (LMIs) to measles and streptokinase/streptodornase (SKSD) were measured at 3- to 6-month intervals and at time of exacerbation in the index case. There were 36 exacerbations in 25 patients. Mean baseline antibody titers and LMI to measles were higher in cases than in controls. No consistent changes occurred in antibody titers to any of the viruses, non in LMI to SKSD. LMIs to measles were lower in most MS patients during exacerbations than before or after exacerbations. This apparent improvement in cell-mediated immune response to measles only during exacerbations may reflect aberrant immune regulation in MS patients, response to recrudescence of a latent agent, or some other phenomenon as yet undefined.

Antibody Formation↗

Measles antibody titers in multiple sclerosis patients and HLA-matched and unmatched siblings.

Antibody titers to measles, cytomegalovirus, and herpesviruses 1 and 2 were compared for siblings of multiple sclerosis (MS) patients sharing two, one, and no histocompatibility antigen haplotypes with the case. Significant differences were observed only for measles. Titers were significantly lower in siblings sharing no haplotypes with the case. Within case-sibling pairs, the presence of HLA-A-A3 and/or B7 affected measles antibody titers more than the presence of MS. These findings suggest that the immune response to measles in these sibships is influenced by the presence of HLA-A-A3 and/or B7 as well as another familial factor.

Adult↗

Intraamniotic infection due to group G streptococcus: treatment and antibody response.

Penicillin treatment and antibody response were studied using a rhesus monkey model for intraamniotic infection with type III group B streptococci (T3GBS). Acute and convalescent phase sera from mothers and their offspring were tested with a radioactive antigen-binding assay to determine the concentration of antibody to the capsular T3GBS antigen. The frequency of placentitis was significantly lower in penicillin-treated animals (3 of 8) than in controls (10 of 10; P less than .01). The penicillin group also had a significantly lower neonatal mortality (1 of 9) than controls (6 of 10; P less than .05). Both groups of rhesus mothers developed a significant increase in concentration of antibody to T3GBS, but the antibody response was of lesser magnitude in the penicillin-treated group. This experimental model appears to be useful for studying both therapy for intraamniotic infection and the humoral immune response to infection with T3GBS.

Amnion↗

Management of genital herpes simplex virus infection during pregnancy.

The clinical course and outcome of 58 pregnancies in 57 women with culture-verified genital herpes simplex virus (HSV) infection during gestation are reported. In 19 cases (33%) an active genital HSV infection was present within 1 week of delivery. Of the 60 infants delivered, 58 survived. No maternal or perinatal morbidity or mortality was attributable to HSV. This experience suggests that weekly culturing of the cervix and all other previously infected genital sites from the 36th week of gestation until delivery is an acceptable plan for managing such pregnancies. Women without evidence of infection at the onset of labor can be allowed to deliver vaginally. With appropriate precautions, breast-feeding by mothers with genital HSV infections is not contraindicated.

Breast Feeding↗